PROJECT SUMMARY ? PULMONARY TOXICOLOGY FACILITY The overarching goal of the Pulmonary Toxicology Facility (PTF) is to provide the facilities and expertise for investigators to enhance the productivity and quality of their pulmonary toxicology research and to assist them in exploring new investigative areas in asthma, pulmonary biology, inhalation toxicology, and aerosol science. Investigators are also supported with expertise and assays to evaluate exposures to rural airborne toxicants, asthma triggers and microorganism-associated molecular patterns such as bacterial endotoxin and fungal glucans in environmental epidemiology studies. The PTF is an extremely productive and highly interactive facility that plays an indispensable role in advancing rural environmental health and the Thematic Areas, Pilot Grant Program and Career Development Program of the EHSRC. Through rigorous and transformative research, the PTF expands the body of knowledge on inhaled toxicants applying innovative exposure systems and methodology. The PTF conducts studies to elucidate adverse outcome pathways for inhaled environmentally-relevant toxicants and multipollutant mixtures. The PTF has the equipment and staff expertise to provide investigators with validated methods and authenticated biological reagents for addressing novel hypotheses regarding pulmonary exposures, lung biology and biological response profiles. The PTF provides services free of charge to recipients of EHSRC pilot grants and Associate Members receiving salary support from the Career Development Program. Other EHSRC Members, NIEHS intramural researchers and members of NIEHS-funded centers at other institutions receive discounted rates. The institutional commitment to the facility is spectacular with a $2,286,280 commitment for newly renovated facilities in the heart of the biomedical campus plus additional instrumentation. In the current cycle, the PTF has served 83 investigators on 81 projects with 46,304 exposure and biomarker assays, 1,426 experimental animals, 990 toxicology procedures, and has deployed and received 8,479 field samplers. Six specific aims will be addressed in the proposed scope of work: Aim 1) Provide expertise and facilities for the use of animal models to elucidate adverse outcome pathways of xenobiotics or to test novel inhalation therapies; Aim 2) Design and perform inhalation exposure studies to groups of laboratory animals under rigidly controlled exposure conditions; Aim 3) Assess biomarkers and sensitive physiologic endpoints to identify biological response profiles, low-dose functional changes, and susceptibility factors; Aim 4) Provide high-content in vitro studies using pulmonary epithelial cells exposed at the air-liquid interface; Aim 5) Perform exposure assessment of endotoxins, glucans, allergens, and metagonomics of microbial communities in support of epidemiologic studies of environmental lung diseases; and Aim 6) Facilitate pre-doctoral, post-doctoral and Associate Member training. The vast array of services provided by the PTF are crucial to meeting EHSRC goals and advancing NIEHS priorities as articulated in their strategic plan.